Research & Scholarship

Clinical Trials

The Reproductive Medicine Network (RMN) is a nationwide cooperative network of 7 clinical
sites and a data coordination center, and is sponsored in 5 year increments by The Eunice
Kennedy Shriver National Institute for Child Health and Human Development (NICHD). The RMN
is charged with designing, implementing and publishing high quality clinical research in
reproductive medicine. It has been in existence for over 15 years and has performed several
seminal clinical trials that have fundamentally changed clinical practice in this field. In
addition, many worthy ancillary protocols have been generated and published.
It is this latter fact, as well as the continued interest by investigators both inside and
outside the RMN for access to DNA or serum samples from the previously performed trials,
that has motivated the present investigators to proactively begin a biologic samples
repository from the ongoing and pending RMN clinical trials. Ideally, this repository would
allow investigators to seamlessly access trial samples for many years into the future, and
thus greatly amplify the use of resources and the impact of the RMN.

The objective of the Males, Antioxidants, and Infertility (MOXI) Trial is to examine whether
treatment of infertile males with an antioxidant formulation improves male fertility. The
central hypothesis is that treatment of infertile males with antioxidants will improve sperm
structure and function, resulting in higher fertilization rates and improved embryo
development, leading to higher pregnancy and live birth rates. Findings from this research
will be significant in that they will likely lead to an effective, non-hormonal treatment
modality for male infertility. An effective treatment for men would also reduce the
treatment burden on the female partner, lower costs, and provide effective alternatives to
couples with religious or ethical contraindications to ART (Assisted Reproductive
Technology). If antioxidants do not improve pregnancy rates, but do improve sperm motility
and DNA integrity, they could allow for couples with male factor infertility to use less
intensive therapies such as intrauterine insemination. Male fertility specialists currently
prescribe antioxidants based on the limited data supporting their use. A negative finding,
lack of any benefit, would also alter current treatment of infertile males.

Stanford is currently not accepting patients for this trial.For more information, please contact Oshra Sedan, PhD, 408-688-9892.

Abstract

To determine whether men with azoospermia are at an elevated risk of developing cancer in the years following an infertility evaluation.Cohort study.United States andrology clinic.A total of 2,238 men with complete records were evaluated for infertility at a single andrology clinic in Texas from 1989 to 2009.None.Cancer incidence was determined by linkage to the Texas Cancer Registry.In all, 451 men had azoospermia, and 1,787 were not azoospermic, with a mean age at infertility evaluation of 35.7 years. Compared with the general population, infertile men had a higher risk of cancer, with 29 cases observed compared with 16.7 expected (standardized incidence rate [SIR] 1.7, 95% confidence interval [CI] 1.2-2.5). When stratifying by azoospermia status, azoospermic men had an elevated risk of cancer (SIR 2.9, 95% CI 1.4-5.4). Infertile men without azoospermia had a trend toward a higher rate of cancer (SIR 1.4, 95% CI 0.9-2.2). The Cox regression model revealed that azoospermic men had 2.2-fold higher cancer risk compared with nonazoospermic men (hazard ratio 2.2, 95% CI 1.0-4.8).Men with azoospermia have an increased risk of subsequently developing cancer, suggesting a possible common etiology between azoospermia and cancer development. Additional follow-up of azoospermic men after reproductive efforts end may be warranted.

Abstract

An estimated 7 million American couples per year seek infertility care in the United States. A male factor contributes to 50% of cases but it is unclear what proportion of infertile couples undergoes male evaluation.We analyzed data from cycles 5 to 7 of the National Survey of Family Growth performed by the Centers for Disease Control to determine the frequency of a male infertility evaluation, and associated reproductive and demographic factors.A total of 25,846 women and 11,067 men were surveyed. Male evaluation was not completed in 18% of couples when the male partner was asked vs 27% when female partners were asked. This corresponds to approximately 370,000 to 860,000 men in the population who were not evaluated at the time of infertility evaluation. Longer infertility duration and white race were associated with increased odds of male infertility evaluation. The male and female samples showed no change in the receipt of male examination with time.Many men from infertile couples do not undergo male evaluation in the United States. Given the potential implications to reproductive goals and male health, further examination of this pattern is warranted.

Abstract

In recent years, investigators have noted a trend toward a declining proportion of male births in many industrialized nations. While men bear the sex-determining chromosome, the role of the female partner as it pertains to fertilization or miscarriage may also alter the gender ratio. We attempted to determine a man's secondary sex ratio (F1 generation) by directly examining the sex chromosomes of his sperm. We examined our male infertility clinic database for all men who had undergone a semen fluorescence in situ hybridization (FISH). Patient demographic and semen parameters were recorded. Chi-squared analysis was used to compare gender ratios (Y chromosomes/total chromosomes). Multivariable logistic regression was used to predict the odds of possessing a Y-bearing sperm after accounting for demographic and semen parameters. A total of 185 men underwent sperm FISH. For the entire cohort, the proportion of Y chromosome-bearing sperm was 51.5%. Men with less than five million motile sperm had a significantly lower proportion of Y chromosome-bearing sperm (50.8%) compared to men with higher sperm counts (51.6%; P=0.02). After multivariable adjustment, a higher sperm concentration, total motile sperm count and semen volume significantly increased the odds of having a Y chromosome-bearing sperm (P<0.01). As a man's sperm production declines, so does the proportion of Y chromosome-bearing sperm. Thus, a man's reproductive potential may predict his ability to sire male offspring.

Abstract

Anogenital distance is a marker for endocrine disruption in animal studies in which decreased distance has been associated with testicular dysfunction. In this study we investigated whether anogenital distance was associated with reproductive hormone levels in adult men.A total of 116 men (mean age 36.1 ± 8.0 years) were evaluated at an andrology clinic in Houston. Anogenital distance (the distance from the posterior aspect of the scrotum to the anal verge) and penile length were measured using digital calipers. Testis size was estimated by physical examination. Linear regression was used to determine correlations between genital measurements and hormone levels.Anogenital distance (r = 0.20, p = 0.03) and penile length (r = 0.20, p = 0.03) were significantly associated with serum testosterone levels while total testis size was not (r = 0.17, p = 0.07). No relationship between genital length and luteinizing hormone, follicle-stimulating hormone or estradiol was identified. After adjusting for age the serum testosterone increased by 20.1 ng/dl (95% CI 1.8, 38.4; p = 0.03) for each 1 cm increase in anogenital distance. On multivariable models no statistically significant relationship existed between penile length and testosterone levels. Moreover men with hypogonadal testosterone levels (less than 300 ng/dl) had a significantly shorter anogenital distance compared to men with higher testosterone levels (31.6 vs 37.3 mm, p = 0.02).Anogenital distance may provide a novel metric to assess testicular function in men. Assuming that anogenital distance at birth predicts adult anogenital distance, our findings suggest a fetal origin for adult testicular function.

Abstract

Fertility potential and reproductive fitness may reflect a man's future health, given that over one-third of the male human genome is involved in reproduction. We sought to determine if offspring number predicts cardiovascular death in the US men.Using data from the NIH-AARP Diet and Health Study, 137,903 men (aged 50-71) without prior cardiovascular disease were followed-up for an average of 10.2 years. International Classification of Diseases, ninth edition, codes were used to establish the cause of death, and multivariable Cox proportional hazards modeling was used to estimate the association between offspring number and cardiovascular death while accounting for sociodemographic and lifestyle characteristics.Almost all (92%) participants had fathered at least one child and 50% had three or more offspring. A total of 3082 men died of cardiovascular causes during follow-up for an age-adjusted incidence rate of 2.70 per 1000 person-years. Compared with fathers, after adjusting for sociodemographic and lifestyle factors, childless men had a 17% [hazard ratio (HR): 1.17; 95% confidence interval (CI): 1.03-1.32] increased risk of death from cardiovascular disease contracted in the study period, and this elevated risk appeared to extend also to men with only one child. In comparison with fathers of five or more children, adjusted relative hazards for cardiovascular mortality of this sort were 1.06 (95% CI: 0.92-1.22) for four children, 1.02 (0.90-1.16) for three children, 1.02 (0.90-1.16) for two children, 1.11 (0.95-1.30) for one child and 1.21 (1.03-1.41) for no children.Married men who have no children have a higher risk of dying from cardiovascular disease contracted after the age of 50 than men with two or more children.

Abstract

To determine whether male and female subfecundity is associated with the gender ratio.Retrospective cohort study.Reproductive endocrinology clinics in California.A cohort of 30,448 women who sought infertility treatment or evaluation in California between 1990 and 1998 was identified. A fertile comparison group was assembled after matching data from vital statistics records.Not applicable.Multivariate logistic regression was used to determine the odds of a male birth based on fertility status.We identified 5,293 infertile women and 6,730 fertile matched women in the live-birth and fetal death records. There were 6,178 children born to women evaluated and/or treated for infertility, compared with 9,131 born to fertile women, for a total of 15,309 births. There was no significant difference in the secondary sex ratio between births in the infertile cohort and the fertile cohort or on the basis of male factor infertility versus female factor infertility. After controlling for confounding factors, there was no difference in sex ratio based on the use of advanced reproductive technologies, duration of infertility treatment, or the type of infertility.This study found no statistical evidence to support an association between infertility and secondary sex ratio.

Abstract

Anogenital distance (AGD), a sexually dimorphic measure of genital development, is a marker for endocrine disruption in animal studies and may be shorter in infant males with genital anomalies. Given the correlation between anogenital distance and genital development, we sought to determine if anogenital distance varied in fertile compared to infertile adult men.A cross sectional study of consecutive men being evaluated for infertility and men with proven fertility was recruited from an andrology clinic. Anogenital distance (the distance from the posterior aspect of the scrotum to the anal verge) and penile length (PL) were measured using digital calipers. ANOVA and linear regression were used to determine correlations between AGD, fatherhood status, and semen analysis parameters (sperm density, motility, and total motile sperm count).A total of 117 infertile men (mean age: 35.3±17.4) and 56 fertile men (mean age: 44.8±9.7) were recruited. The infertile men possessed significantly shorter mean AGD and PL compared to the fertile controls (AGD: 31.8 vs 44.6 mm, PL: 107.1 vs 119.5 mm, p<0.01). The difference in AGD persisted even after accounting for ethnic and anthropomorphic differences. In addition to fatherhood, on both unadjusted and adjusted linear regression, AGD was significantly correlated with sperm density and total motile sperm count. After adjusting for demographic and reproductive variables, for each 1 cm increase in a man's AGD, the sperm density increases by 4.3 million sperm per mL (95% CI 0.53, 8.09, p?=?0.03) and the total motile sperm count increases by 6.0 million sperm (95% CI 1.34, 10.58, p?=?0.01). On adjusted analyses, no correlation was seen between penile length and semen parameters.A longer anogenital distance is associated with fatherhood and may predict normal male reproductive potential. Thus, AGD may provide a novel metric to assess reproductive potential in men.

Abstract

Fatherhood status has been hypothesized to affect prostate cancer risk but the current evidence is limited and contradictory.We prospectively evaluated the relationship between offspring number and the risk of prostate cancer in 161,823 men enrolled in the National Institues of Health - American Association of Retired Persons Diet and Health Study. Participants were aged 50-71 years without a cancer diagnosis at baseline in 1995. Analysing 8134 cases of prostate cancer, Cox regression was used to estimate the association between offspring number and prostate cancer incidence while accounting for socio-demographic and lifestyle characteristics.When examining the entire cohort, there was no relationship between fatherhood and incident prostate cancer [hazard ratio (HR) 0.94, 95% confidence interval (CI) 0.86-1.02]. However, after stratifying for prostate cancer screening, prostate-specific antigen (PSA) unscreened childless men had a lower risk of prostate cancer (HR 0.73, 95% CI 0.58-0.91) compared with fathers due to the interaction between PSA screening and fatherhood (P for interaction?< 0.01). A trend for the lower risk of prostate cancer among unscreened fathers compared with childless men was seen for low-grade prostate cancer (HR 0.78, 95% CI 0.61-1.01), high-grade prostate cancer (HR 0.62, 95% CI 0.37-1.04) and even fatal prostate cancer (HR 0.28, 95% CI 0.07-1.12). The number of children fathered was not related to prostate cancer (P(trend)?= 0.17). In addition, men's inability to sire female offspring showed a weak positive association with prostate cancer in the PSA unscreened study subjects.Our findings suggest fatherhood status and offspring gender is associated with a man's prostate cancer risk.

Estimating the Number of Vasectomies Performed Annually in the United States: Data From the National Survey of Family GrowthJOURNAL OF UROLOGYEisenberg, M. L., Lipshultz, L. I.2010; 184 (5): 2068-2072

Abstract

While hospital discharge and ambulatory surgery registries provide accurate estimates of female sterilization procedures, current estimates of male sterilization rates are lacking since these procedures are done in many settings. Population based data are used to estimate annual sterilization numbers.We analyzed data on 4,928 men and 7,643 women from the 2002 National Survey of Family Growth. We determined the year of vasectomy in men and the year of tubal ligation in women who reported a history of surgical sterilization. After accounting for the complex survey design of the National Survey of Family Growth we calculated the estimated number of individuals who underwent surgical sterilization in the United States.A total of 141 men reported vasectomy, representing an overall 6% prevalence in National Survey of Family Growth survey population, while 1,173 women (16%) reported tubal ligation. Using National Survey of Family Growth data an estimated 175,000 to 354,000 vasectomies were done yearly from 1998 to 2002. In the same period the National Survey of Family Growth estimated that 546,000 to 789,000 tubal ligations were done annually in the United States. This compares closely to the 596,000 to 687,000 tubal ligations calculated using ambulatory surgery and hospital discharge data from a similar period.The estimated annual number of tubal ligations from the National Survey of Family Growth is in line with the current literature using hospital discharge and ambulatory surgery registries, suggesting the accuracy of the method of estimating surgical sterilization numbers. This suggests that the National Survey of Family Growth may be used to provide an estimate of vasectomy use in the United States.

Abstract

It has been reported that fatherhood status may be a risk factor for prostate cancer. In the current study, the authors examined the subsequent occurrence of prostate cancer in a cohort of men evaluated for infertility to determine whether male infertility is a risk factor for prostate cancer.A total of 22,562 men who were evaluated for infertility from 1967 to 1998 were identified from 15 California infertility centers and linked to the California Cancer Registry. The incidence of prostate cancer was compared with the incidence in an age-matched and geography-matched sample of men from the general population. The risk of prostate cancer in men with and those without male factor infertility was modeled using a Cox proportional hazards regression model.A total of 168 cases of prostate cancer that developed after infertility were identified. Men evaluated for infertility but not necessarily with male factors were not found to have an increased risk of cancer compared with the general population (standardized incidence ratio [SIR], 0.9; 95% confidence interval [95% CI], 0.8-1.1). This risk was found to be highest for men with male factor infertility who developed high-grade prostate cancer (SIR, 2.0; 95% CI, 1.2-3.0). On multivariate analyses, men with male factor infertility were found to be 2.6 times more likely to be diagnosed with high-grade prostate cancer (hazard ratio, 2.6; 95% CI, 1.4-4.8).Men with male factor infertility were found to have an increased risk of subsequently developing high-grade prostate cancer. Male infertility may be an early and identifiable risk factor for the development of clinically significant prostate cancer.

Abstract

What is the relationship between couple's health and fecundity in a preconception cohort?Somatic health may impact fecundity in men and women as couples whose male partner had diabetes or whose female partner had two or more medical conditions had a longer time-to-pregnancy (TTP).The impact of somatic health on human fecundity is hypothesized given the reported declines in spermatogenesis and ovulation among individuals with certain medical comorbidities.A population-based prospective cohort study recruiting couples from 16 counties in Michigan and Texas (2005-2009) using sampling frameworks allowing for identification of couples planning pregnancy in the near future. Five hundred and one couples desiring pregnancy and discontinuing contraception were followed-up for 12 months or until a human chorionic gonadotropin pregnancy was detected.In all, 33 (21.4%) female and 41 (26.6%) male partners had medical conditions at baseline.Couples' medical comorbidity was associated with pregnancy status. Diabetes in either partner was associated with diminished fecundity, as measured by a longer TTP. Specifically, fecundability odds ratios (FORs) were below 1, indicating a longer TTP, for male partners with diabetes (0.35, 95% confidence interval (CI): 0.14-0.86) even in adjusted models (0.35, 95% CI: 0.13-0.88). Female partners with diabetes had comparable reductions in FORs; however, the analyses did not reach statistical significance (0.26, 95% CI: 0.03-1.98). Female partners with two or more medical conditions had a significantly longer TTP compared with women with no health problems (0.36, 95% CI: 0.14-0.92). Importantly, the presence of medical conditions was not associated with sexual frequency. We cannot rule out residual confounding, Type 2 errors for less prevalent medical conditions, or chance findings in light of the multiple comparisons made in the analysis.The findings require cautious interpretation given that medical diagnoses are subject to possible reporting errors, although we are unaware of any potential biases that may have been introduced, as participants were unaware of how long it would take to become pregnant upon enrollment.The current report suggests a relationship between male and female diabetes and fecundity, and possibly somatic health more globally. Moreover, while the mechanism is uncertain, if corroborated, our data suggest that early evaluation and treatment may be warranted for diabetics prior to attempting to conceive.Intramural research of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (Contract nos. #N01-HD-3-3355, N01-HD-3-3356 and N01-HD-3-3358). The authors have no conflicts of interest to declare.

Abstract

Testosterone supplementation therapy (TST) has become increasingly popular since the turn of the century. Most prescriptions in the U.S. are written by primary care providers, endocrinologists, or urologists. The FDA has requests pharmaceutical companies provide more long term data on efficacy and safety of testosterone products. Results from these studies will help define the appropriate population for TST going forward. It is hoped that these data combined with physician and public education will minimize inappropriate prescribing and allow those likely to benefit from TST to receive it.

Abstract

As couples are increasingly delaying parenthood, the effect of the aging men and women on reproductive outcomes has been an area of increased interest. Advanced paternal age has been shown to independently affect the entire spectrum of male fertility as assessed by reductions in sperm quality and fertilization (both assisted and unassisted). Moreover, epidemiological data suggest that paternal age can lead to higher rates of adverse birth outcomes and congenital anomalies. Mounting evidence also suggests increased risk of specific pediatric and adult disease states ranging from cancer to behavioral traits. While disease states associated with advancing paternal age have been well described, consensus recommendations for neonatal screening have not been as widely implemented as have been with advanced maternal age.

Abstract

Controversy exists regarding stability of semen quality over time with papers reporting decrease, increase or stable parameters in heterogeneous populations. The current study examined semen parameters of young adult men from 2003 to 2013 at an urban U.S. sperm bank. Semen parameters were analyzed before and after cryopreservation for a total of 9425 specimens from 489 individuals. Demographic information was obtained from a social and medical history questionnaire. Following 2-3 days abstinence, the specimens were collected at the laboratory and assessed by uniform technicians and techniques. The data were analyzed using generalized linear regression after adjustment for age, days of abstinence, for repeated samples, as well as by the Cochran-Armitage trend test. The within variability was accounted for by the repeated measures model. All p values were two-sided with p

Abstract

To determine the incidence of chronic medical conditions of men with infertility.Retrospective cohort study.Not applicable.Subjects contained within the Truven Health MarketScan claims database from 2001 to 2009.Not applicable.The development of chronic medical conditions including hypertension, diabetes, hyperlipidemia, renal disease, pulmonary disease, liver disease, depression, peripheral vascular disease, cerebrovascular disease, heart disease, injury, alcohol abuse, drug abuse, anxiety disorders, and bipolar disorder.In all, 13,027 men diagnosed with male factor infertility were identified with an additional 23,860 receiving only fertility testing. The average age was 33.1 years for men diagnosed with infertility and 32.8 years for men receiving testing alone. After adjusting for confounding factors, men diagnosed with male factor infertility had a higher risk of developing diabetes (hazard ratio [HR] 1.30, 95% confidence interval [CI] 1.10-1.53), ischemic heart disease (HR 1.48, 95% CI 1.19-1.84), alcohol abuse (HR 1.48, 95% CI 1.07-2.05), and drug abuse (1.67, 95% CI 1.06-2.63) compared with men who only received infertility testing. Similar patterns were identified when comparing those with male factor infertility to vasectomized men. The association between male factor infertility and later health outcomes were strongest for men with longer follow-up.In this cohort of patients in a national insurance database, men diagnosed with male factor infertility had a significantly higher risk of adverse health outcomes in the years after an infertility evaluation. These findings suggest the overall importance of men's reproductive health and warrant additional investigation to understand the association and identify interventions to improve outcomes for these patients.

Abstract

It is predicted that Japan and European Union will soon experience appreciable decreases in their populations due to persistently low total fertility rates (TFR) below replacement level (2.1 child per woman). In the United States, where TFR has also declined, there are ethnic differences. Caucasians have rates below replacement, while TFRs among African-Americans and Hispanics are higher. We review possible links between TFR and trends in a range of male reproductive problems, including testicular cancer, disorders of sex development, cryptorchidism, hypospadias, low testosterone levels, poor semen quality, childlessness, changed sex ratio, and increasing demand for assisted reproductive techniques. We present evidence that several adult male reproductive problems arise in utero and are signs of testicular dysgenesis syndrome (TDS). Although TDS might result from genetic mutations, recent evidence suggests that it most often is related to environmental exposures of the fetal testis. However, environmental factors can also affect the adult endocrine system. Based on our review of genetic and environmental factors, we conclude that environmental exposures arising from modern lifestyle, rather than genetics, are the most important factors in the observed trends. These environmental factors might act either directly or via epigenetic mechanisms. In the latter case, the effects of exposures might have an impact for several generations post-exposure. In conclusion, there is an urgent need to prioritize research in reproductive physiology and pathophysiology, particularly in highly industrialized countries facing decreasing populations. We highlight a number of topics that need attention by researchers in human physiology, pathophysiology, environmental health sciences, and demography.

Abstract

To identify differences in demographic and socio-economic factors between men seeking infertility evaluation and those undergoing vasectomy, to address disparities in access to these services.Data from Cycle 6 and Cycle 7 (2002 and 2006-2008) of the National Survey of Family Growth (NSFG) were reviewed. The NSFG is a multistage probability survey designed to capture a nationally representative sample of households with men and women aged 15-45 years in the USA. The variables analysed included age, body mass index, self-reported health, alcohol use, race, religious affiliation, marital status, number of offspring, educational attainment, income level, insurance status and metropolitan home designation. Our primary outcome was the correlation of these demographic and socio-economic factors with evaluation for male infertility or vasectomy.Of the 11 067 men identified through the NSFG, 466 men (4.2%) sought infertility evaluation, representing 2 187 455 men nationally, and 326 (2.9%) underwent a vasectomy, representing 1 510 386 men nationally. Those seeking infertility evaluation were more likely to be younger and have fewer children (P = 0.001, 0.001) and less likely to be currently married (78 vs 74%; P = 0.010) or ever married (89 vs 97%; P = 0.002). Men undergoing a vasectomy were more likely to be white (86 vs 70%; P = 0.001). Men seeking infertility evaluation were more likely to have a college or graduate degree compared with men undergoing a vasectomy (68 vs 64%; P = 0.015). There was no difference between the two groups for all other variables.While differences in demographic characteristics such as age, offspring number and marital status were identified, measures of health, socio-economic status, religion and insurance were similar between men undergoing vasectomy and those seeking infertility services. These factors help characterize the utilization of male reproductive health services in the USA and may help address disparities in access to these services and improve public health strategies.

Abstract

To study the relationship among occupation, health, and semen quality in a cohort of men attempting to conceive.Observational prospective cohort.Not applicable.A total of 501 couples discontinuing contraception were followed for 1 year while trying to conceive; 473 men (94%) provided one semen sample, and 80% provided a second sample.None.Semen data obtained through at-home semen collection with next-day analysis/quantification.In all, complete data were available for 456 men, with a mean age of 31.8 years. Work-related heavy exertion was consistently associated with lower semen concentration and total sperm count. Thirteen percent of men who reported heavy exertion displayed oligospermia, compared with 6% who did not report workplace exertion. Shift work, night work, vibration, noise, heat, and prolonged sitting were not associated with semen quality. Men with high blood pressure had significantly lower strict morphology scores compared with normotensive men (17% vs. 21%). In contrast, hyperlipidemia, diabetes, and composite of total comorbidities were not associated with semen quality. The number of medications a man was taking as a proxy of health status was associated with semen quality. There was a negative association between number of medications and sperm count.A negative relationship among occupational exertion, hypertension, and the number of medications with semen quality was identified. As these are potentially modifiable factors, further research should determine whether treatment or cessation may improve male fecundity.

Abstract

Aberrations in reproductive fitness may be a harbinger of medical diseases in men. Data suggest a higher risk of testicular cancer in infertile men. However, the relationship between infertility and other cancers remains uncertain.We analyzed subjects from the Truven Health MarketScan® claims database from 2001 to 2009. Infertile men were identified through diagnosis and treatment codes. Comparison groups were created of men who underwent vasectomy and a control cohort of men who were not infertile and had not undergone vasectomy. The incidence of cancer was compared to national U.S. estimates. Infertile men were also compared to men who underwent vasectomy and the control cohort using a Cox regression model.A total of 76,083 infertile men were identified with an average age of 35.1 years. Overall 112,655 men who underwent vasectomy and 760,830 control men were assembled. Compared to age adjusted national averages, infertile, vasectomy and control subjects in the study cohorts had higher rates of all cancers and many individual cancers. In time to event analysis, infertile men had a higher risk of cancer than those who underwent vasectomy or controls. Infertile men had a higher risk of testis cancer, nonHodgkin lymphoma and all cancers than the vasectomy and control groups.Consistent with prior reports, we identified an increased risk of testicular cancer in infertile men. The current data also suggest that infertile men are at a mildly increased risk of all cancers in the years after infertility evaluation. Future research should focus on confirming these associations and elucidating pathways between infertility and cancer.

Abstract

In humans, recent studies have correlated anogenital distance (AGD) in adult men to testicular function. While studies of a group of men suggest an association, the utility of AGD in an infertility evaluation remains uncertain. We sought to determine the utility of AGD to predict male fertility.Between 2010 and 2011, men were recruited at a urology clinic to participate. AGD was measured using digital calipers in men being evaluated at a urology clinic. ANOVA and ROC analyses were used to determine correlations between AGD, fatherhood status, and semen parameters.In all, 473 men were included in the analysis with a mean age of 43 ± 13 years. Anogenital distance was significantly longer in men with higher sperm concentration, total sperm count, and total motile sperm count. In order to evaluate the discriminating ability of AGD, ROC curves were created comparing AGD and total testis volume. The area under the curve (AUC) was significantly larger for total testis volume compared to AGD when evaluating fertility (0.71 vs 0.63, p = 0.02). Similarly, there was a trend towards a higher AUC for testis volume compared to AGD for sperm concentration and total sperm count. Stratification of men with long/short AGD and large/small testes also did not improve the predictive value of AGD.While AGD is associated with sperm production on a population level, at the individual level the distinction based AGD alone cannot accurately estimate the efficiency of spermatogenesis.

Abstract

Recent data suggest an increased risk of cardiovascular events and mortality in men on testosterone therapy (TT). To date, there are no long-term, prospective studies to determine safety. In such cases, retrospective observational studies can be helpful. We examined our patient database to determine whether TT altered the risk of all-cause mortality in men. We queried our hormone database for all men with a serum testosterone level and then examined charts to determine testosterone status. In all, 509 men had charts available for review. We linked our patient records to the National Death Index to determine mortality. Of the 509 men who met inclusion criteria, 284 were on TT and 225 did not use testosterone. Age (mean 54 years) and follow-up time (mean 10 years) were similar for both groups. In all, 19 men died--10 (4.4%) men not on TT and 9 (3.2%) men on TT. After adjusting for age and year of evaluation, there was no significant difference in the risk of death based on TT (hazard ratio 0.92, 95% confidence interval 0.36-2.35, P=1.0). There appears to be no change in mortality risk overall for men utilizing long-term testosterone therapy.

Abstract

To determine if testosterone therapy (TT) status modifies a man's risk of cancer.The Urology clinic hormone database was queried for all men with a serum testosterone level and charts examined to determine TT status. Patient records were linked to the Texas Cancer Registry to determine the incidence of cancer. Men accrued time at risk from the date of initiating TT or the first office visit for men not on TT. Standardised incidence rates and time to event analysis were performed.In all, 247 men were on TT and 211 did not use testosterone. In all, 47 men developed cancer, 27 (12.8%) were not on TT and 20 (8.1%) on TT. There was no significant difference in the risk of cancer incidence based on TT (hazard ratio [HR] 1.0, 95% confidence interval [CI] 0.57-1.9; P = 1.8). There was no difference in prostate cancer risk based on TT status (HR 1.2, 95% CI 0.54-2.50).There was no change in cancer risk overall, or prostate cancer risk specifically, for men aged >40 years using long-term TT.

Abstract

To study the relationship between semen quality and current health status in a cohort of men evaluated for infertility.Cross-sectional study.Fertility clinic.Nine thousand three hundred eighty-seven men evaluated for infertility between 1994 and 2011.None.Charlson comorbidity index, medical diagnoses by organ system.At the time of evaluation, 9,387 men with a mean age of 38 years had semen data available. Of these men, 44% had at least one medical diagnosis unrelated to infertility. When stratifying the cohort by the Charlson comorbidity index (CCI), differences in all measured semen parameters were identified. Men with a higher CCI had lower semen volume, concentration, motility, total sperm count, and morphology scores. In addition, men with diseases of the endocrine, circulatory, genitourinary, and skin diseases all showed significantly higher rates of semen abnormalities. Upon closer examination of diseases of the circulatory system, men with hypertensive disease, peripheral vascular and cerebrovascular disease, and nonischemic heart disease all displayed higher rates of semen abnormalities.The current report identified a relationship between medical comorbidites and male semen production. Although genetics help guide a man's sperm production, his current condition and health play an important role.

Abstract

What is the relationship between semen parameters and mortality in men evaluated for infertility?Among men undergoing an infertility evaluation, those with abnormal semen parameters have a higher risk of death, suggesting a possible common etiology between infertility and mortality.Conflicting data exist that suggest either an inverse relationship or no relationship between semen quality and mortality.A study cohort was identified from two centers, each specializing in infertility care. In California, we identified men with data from 1994 to 2011 in the Stanford Reproductive Endocrinology and Infertility semen database. In Texas, we identified men with data from 1989 to 2009 contained in the andrology database at the Baylor College of Medicine Special Procedures Laboratory who were evaluated for infertility. Mortality was determined by data linkage to the National Death Index or Social Security Death Index. Comorbidity was estimated based on calculation of the Charlson Comorbidity Index or Centers for Medicare & Medicaid Services-Hierarchical Condition Categories Model.In all, 11,935 men were evaluated for infertility from 1989 to 2011. During 92 104 person years of follow-up, 69 of 11,935 men died (0.58%). The mean age at infertility evaluation was 36.6 years with a mean follow-up of 7.7 years.Compared with the general population, men evaluated for infertility had a lower risk of death with 69 deaths observed compared with 176.7 expected (Standardized mortality rate 0.39, 95% CI 0.30-0.49). When stratified by semen parameters, however, men with impaired semen parameters (i.e. male factor infertility) had significantly higher mortality rates compared with men with normal parameters (i.e. no male factor infertility). Low semen volume, sperm concentration, sperm motility, total sperm count and total motile sperm count were all associated with higher risk of death. In contrast, abnormal sperm morphology was not associated with mortality. While adjusting for current health status attenuated the association between semen parameters and mortality, men with two or more abnormal semen parameters still had a 2.3-fold higher risk of death compared with men with normal semen (95% CI 1.12-4.65).Our cohort represents infertile men, which may limit generalizability. As comorbidity relied on administrative data, granular information on each man regarding infertility diagnosis and lifestyle factors was unavailable.Men with impaired semen parameters have an increased mortality rate in the years following an infertility evaluation suggesting semen quality may provide a marker of health.This study is supported in part by P01HD36289 from the Eunice Kennedy Shriver National Institute for Child Health and Human Development, National Institutes of Health (to D.J.L. and L.I.L.). The project was also partially supported by an NIH CTSA award number UL1 RR025744. None of the authors has any conflict of interest to declare.

Abstract

Is parental age at delivery associated with a man's semen quality?In this large register-based study both mother's and father's age are found to have minimal effects on semen quality in men.Both maternal and paternal age have been associated with a range of adverse health effects in the offspring. Given the varied health effects of parental age upon offspring, and the sensitivity of genital development to external factors, it is plausible that the age of a man's mother and father at conception may impact his reproductive health. To our knowledge this is the first examination of the effects of parental age on semen quality.A retrospective cohort study of 10 965 men with semen data and parental data.The study was based on Danish men referred to the Copenhagen Sperm Analysis Laboratory due to infertility in their partnership. Men born from 1960 and delivering a semen sample until year 2000 were included. The men were linked to the Danish Civil Registration System to obtain information on parent's age at delivery. Logistic regression analyses were used to calculate odds ratios and 95% confidence intervals for impaired semen quality. Linear regression analyses were used to examine a relationship between semen parameters and paternal age.There were no convincing effect of either mother's or father's age on a man's semen quality. As no trends were noted, the few statistically significant results are likely attributable to chance.Information regarding individual subject characteristics which may impact sperm production (i.e. smoking, BMI) were not available. While our sample size was large, we cannot exclude the possibility that a trend may have been identified with a still larger sample. In addition, the Danish Civil Registration System is merely administrative and hence does not discriminate between biological and adopted children. However, the low rate of adoption (≈2%) suggests that misclassification would have a minimal impact. The men were all referred to the laboratory for infertility problems in their partnership and, therefore, do not represent the general population. We, however, compared semen quality among men within the cohort, and it is therefore less important whether they, in fact, represent the general population.The current study found no link between parental age and a son's semen quality, suggesting other factors may explain recent impairments in men's reproductive health.This work was supported by the Hans and Nora Buchard's Fund and the Kirsten and Freddy Johansen's Fund. No competing interests.Not relevant.

Abstract

What is the relationship between body size, physical activity and semen parameters among male partners of couples attempting to become pregnant?Overweight and obesity are associated with a higher prevalence of low ejaculate volume, sperm concentration and total sperm count.Higher BMI is associated with impaired semen parameters, while increasing waist circumference (WC) is also associated with impaired semen parameters in infertile men.Data from the Longitudinal Investigation of Fertility and the Environment (LIFE) Study were utilized. The LIFE study is a population-based prospective cohort of 501 couples attempting to conceive in two geographic areas (Texas and Michigan, USA) recruited in 2005-2009. Couples were recruited from four counties in Michigan and 12 counties in Texas to ensure a range of environmental exposures and lifestyle characteristics. In person interviews were conducted to ascertain demographic, health and reproductive histories followed by anthropometric assessment.We categorized BMI (kg/m(2)) as <25.0 (underweight and normal), 25.0-29.9 (overweight) 30.0-34.9 (obese, class I) and ≥35 (obese, class II) for analysis. Data were available for analysis in 468 men (93% participation), with a mean ± SD age of 31.8 ± 4.8 years, BMI of 29.8 ± 5.6 kg/m(2) and WC of 100.8 ± 14.2 cm. The majority of the cohort (82%) was overweight or obese with 58% reporting physical activity <1 time/week. The median sperm concentration for the men in the cohort was 60.2 M/ml with 8.6% having oligospermia (<15 M/ml).When examining semen parameters, ejaculate volume showed a linear decline with increasing BMI and WC (P < 0.01). Similarly, the total sperm count showed a negative linear association with WC (P < 0.01). No significant relationship was seen between body size (i.e. BMI or WC) and semen concentration, motility, vitality, morphology or DNA fragmentation index. The percentage of men with abnormal volume, concentration and total sperm increased with increasing body size (P < 0.05). No relationship between physical activity and semen parameters was identified.Our cohort was largely overweight and sedentary, which may result in limited external validity, i.e. generalizability. The lack of physical activity did preclude examination of exercise more frequently than once per week, thus our ability to examine more active individuals is limited.Body size (as measured by BMI or WC) is negatively associated with semen parameters with little influence of physical activity. Our findings are the first showing a relationship between WC and semen parameters in a sample of men without known infertility. Given the worldwide obesity epidemic, further study of the role of weight loss to improve semen parameters is warranted.Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (Contracts #N01-HD-3-3355, N01-HD-3-3356 and N01-HD-3-3358). There are no competing interests.

Abstract

To determine if clinical pregnancy rates and fertilization rates with the use of cryopreserved sperm for intracytoplasmic sperm injection (ICSI) in patients with azoospermia due to spermatogenic dysfunction (i.e., nonobstructive azoospermia) are similar to those with fresh sperm.Systematic review and meta-analysis.Academic medical center.Azoospermic men secondary to spermatogenic dysfunction.Not applicable.Clinical pregnancy rate, fertilization rate.Eleven studies met criteria for the outcome of clinical pregnancy rate. Seventy-nine (28.7%) of 275 intracytoplasmic sperm injection cycles using fresh testicular sperm resulted in a clinical pregnancy, compared with 84 (28.1%) of 299 intracytoplasmic sperm injection cycles using cryopreserved sperm (relative risk [RR] 1.00, 95% confidence interval [CI] 0.75-1.33). Ten studies met criteria for the outcome of fertilization rate. A total of 1,422 (52.9%) of 2,687 oocytes injected with fresh testicular sperm were fertilized, compared with 1,490 (54.0%) of 2,757 oocytes injected with cryopreserved sperm (RR 0.97, 95% CI 0.92-1.02).In men with azoospermia due to spermatogenic dysfunction, there is no statistical difference between the use of fresh versus cryopreserved-thawed testicular sperm when assessing clinical pregnancy or fertilization rates in couples undergoing ICSI.

Abstract

Erectile dysfunction (ED) is more common in men with type 2 diabetes mellitus (T2DM), obesity, and/or the metabolic syndrome (MetS).The aim of this study is to investigate the associations among proxy measures of diabetic severity and the presence of MetS with ED in a nationally representative U.S. data sample.We performed a cross-sectional analysis of adult participants in the 2001-2004 National Health and Nutrition Examination Survey.ED was ascertained by self-report. T2DM severity was defined by calculated measures of glycemic control and insulin resistance (IR). IR was estimated using fasting plasma insulin (FPI) levels and the homeostasis model assessment of IR (HOMA-IR) definition. We classified glycemic control using hemoglobin-A1c (HbA1c) and fasting plasma glucose (FPG) levels. MetS was defined by the American Heart Association and National Heart, Lung, and Blood Institute criteria. Logistic regression models, adjusted for sociodemographics, risk factors, and comorbidities, were fitted for each measure of T2DM severity, MetS, and the presence of ED.Proxy measures of glycemic control and IR were associated with ED. Participants with FPG between 100-126 mg/dL (5.6-7 mmol/L) and ≥ 126 mg/dL (>7 mmol/L) had higher odds of ED, odds ratio (OR) 1.22 (confidence interval or CI, 0.83-1.80), and OR 2.68 (CI, 1.48-4.86), respectively. Participants with HbA1c 5.7-6.4% (38.8-46.4 mmol/mol) and ≥ 6.5% (47.5 mmol/mol) had higher odds of ED (OR 1.73 [CI, 1.08-2.76] and 3.70 [CI, 2.19-6.27], respectively). When FPI and HOMA-IR were evaluated by tertiles, there was a graded relation among participants in the top tertile. In multivariable models, a strong association remained between HbA1c and ED (OR 3.19 [CI,1.13-9.01]). MetS was associated with >2.5-fold increased odds of self reported ED (OR 2.55 [CI, 1.85-3.52]).Poor glycemic control, impaired insulin sensitivity, and the MetS are associated with a heightened risk of ED.

Abstract

Anogenital distance (AGD) is used to define degree of virilization of genital development, with shorter length being associated with feminization and male infertility. The first exon of the androgen receptor (AR) consists of a polymorphic sequence of cytosine-adenine-guanine (CAG) repeats, with longer CAG repeat lengths being associated with decreased receptor function. We sought to determine if there is an association between AGD and AR CAG repeat length. A cross-sectional, prospective cohort of men evaluated at a urology clinic at a single institution was recruited. AGD (the distance from the posterior scrotum to the anal verge) and penile length (PL) were measured. Sanger DNA sequence analysis was used to define CAG repeat length. AGD and CAG repeat lengths in 195 men were determined. On unadjusted analysis, there was no linear relationship between CAG repeat length and PL (P=0.17) or AGD (P=0.31). However, on sub-population analyses, those men with longer CAG repeat lengths (>26) had significantly shorter AGDs compared to men with shorter CAG repeat lengths. For example, the mean AGD was 41.9 vs. 32.4 mm with a CAG repeat length ≤26 vs. >26 (P=0.01). In addition, when stratifying the cohort based on AGD, those with AGD less than the median (i.e. 40 mm) had a longer CAG repeat length compared to men with an AGD >40 mm (P=0.02). In summary, no linear relationship was found between AGD and AR CAG repeat length overall.

Abstract

In humans, recent studies have correlated anogenital distance (AGD) in adult men to intrinsic testicular function. Although rodent studies suggest that AGD is determined in utero and remains constant in adult life, it is not certain if AGD remains constant across a man's adult life. We sought to determine if adult male AGD varies based on age. A cross-sectional study of men being evaluated at a men's health clinic. Anogenital distance (the distance from the posterior aspect of the scrotum to the anal verge) and penile length (PL) were measured using digital callipers. anova and linear regression were used to determine correlations between AGD, fatherhood status and age. In all, 473 men were included in the analysis with a mean age of 43 ± 13 years. The mean AGD for the group was 39 ± 13 mm. Anogenital distance did not vary between age categories for the entire group, for fathers, and for childless men. Moreover, penile length also remained constant across age categories. On adjusted analyses stratified by fatherhood status, there was no relationship between AGDp and age. The current cross-sectional study demonstrates that anogenital distance, defined as the distance from the posterior scrotum to the anal verge, is similar for men of different ages. As such, AGD may provide a measure for genital development and function throughout adult life. However, confirmation with longitudinal studies is needed.

Abstract

Study Type--Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? Anogenital distance (AGD) is a marker of genital development and adult testicular function. To date, there is no data on the clinical utility of using such an anthropomorphic variable. About 30% of men will have no improvement in semen parameters after varicocele repair. It is currently difficult to assess which patients are most likely to benefit from surgical repair. The present study showed that men with a longer AGD had a higher likelihood of improvement after varicocelectomy. As such, AGD may allow clinicians to better counsel men on the efficacy of varicocele repair.• To investigate whether anogenital distance (AGD) can identify men most likely to show improved semen parameters after varicocele ligation, as AGD has been shown to correlate with intrinsic adult testicular function.• Men with varicoceles who were evaluated at a men's reproductive health clinic in Houston were recruited. • AGD (the distance from the posterior aspect of the scrotum to the anal verge) was measured using digital callipers. • Logistic regression was used to compare outcomes after stratifying men based on AGD.• In all, 46 men with a mean (sd) age of 33.1 (6.3) years with postoperative semen data were recruited. • Semen concentration, motility, and total motile sperm count all showed significant improvement postoperatively (P < 0.01). • While 48% of men with a shorter AGD had improvements in sperm concentration postoperatively, 84% of men with a longer AGD improved (P = 0.01). • There was a trend toward a lower percentage of men (62% vs 84%) with shorter AGDs showing improvements in total motile sperm count (P = 0.09).• AGD may provide a novel metric to assess intrinsic testicular function and predict efficacy of varicocele repair.

Abstract

Although controversial, seasonal variations in testosterone have been observed in several populations of men throughout the world. This finding might have an impact on screening and treatment of hypogonadism. We examined the circannual patterns of sex hormones in the Southwest United States. A prospectively assembled database of almost 11 000 patients in a men's health practice was used to collect data on testosterone, estradiol, sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and dehydroepiandrosterone-sulfate (DHEA-S). Patient age, address, and date of visit were recorded. Of note, testosterone-estrogen ratio (T/E ratio) and free testosterone were calculated values. The data were grouped by month and by season (3-month intervals beginning with June, July, and August as summer). Analysis of variance was used to compare hormone levels between seasonal and monthly data sets, with P < .05 regarded as statistical significance. Statistically significant differences in estradiol (P = .02), T/E ratio (P < .01), FSH (P = .02), and SHBG (P < .01) were observed between seasons. Peak-to-trough variations were as follows: 6% for estradiol, 16.5% for T/E ratio, 11.0% for FSH, and 11.6% for SHBG. The T/E ratio peaked in the spring and was at its nadir in the fall. No differences in testosterone (P = .21), LH (P = .25), free testosterone (P = .08), and DHEA-S (P = .11) were observed. Statistically significant evidence of variation in estradiol and T/E ratio were identified in the men included in this study. Although this is consistent with seasonal body habitus changes, physical activity levels, and hypothesized hormonal patterns, the variability reported in the literature makes further trials covering a broader geographic region important to confirm the findings.

Abstract

Anogenital distance (AGD) is a marker for endocrine disruption in animal studies in which decreased male AGD has been associated with testicular dysfunction. The objective of the study was to investigate whether anogenital distance could distinguish men with obstructive azoospermia (OA) from those with nonobstructive azoospermia (NOA). To accomplish this, azoospermic men were recruited and evaluated at a men's reproductive health clinic in Houston, TX. Anogenital distance (the distance from the posterior aspect of the scrotum to the anal verge) and penile length (PL) were measured using digital calipers. Testis size was estimated by physical examination. Logistic regression was used to compare AGD lengths in men with OA and men with NOA. A total of 69 OA men (mean age: 44.2 ± 9.2) and 29 NOA men (mean age: 32.8 ± 4.8) were recruited. The NOA men possessed significantly shorter mean AGD than the men with OA (AGD: 36.3 vs. 41.9 mm, p = 0.01). An AGD of less than 30 mm, had a 91% specificity in accurately classifying NOA. Moreover, after adjustment for age, race, and BMI, an AGD of less than 30 mm yielded a significantly increased odds of NOA compared to OA (OR 5.6, 95% CI 1.0, 30.7). In summary, AGD may provide a novel metric for assessing testicular function in men and in distinguishing OA from NOA.

Abstract

Animal models of endocrine dysfunction have associated male genital defects with reduced anogenital distance (AGD). Human studies have correlated shorter AGD with exposure to putative endocrine disruptors in the environment but have not examined AGD in hypospadiac boys. We measured AGD in boys with hypospadias and those with normal genitals.Data were collected prospectively on boys undergoing urologic procedures at the University of California San Francisco and the Children's Hospital of Oakland, CA, USA. Data included age, race, height, weight, BMI, urologic diagnoses and AGD. To minimize any potential effects of race on observed AGD, we examined only Caucasian boys. Differences between boys with hypospadias and those with normal genitals were examined through two-tailed Student's t-tests.One hundred and nineteen Caucasian boys ranging in age from 4 to 86 months underwent AGD measurement, of which 42 and 77 were boys with normal genitals and hypospadias, respectively. The mean (±SD) AGD of boys with hypospadias was 67 ± 1.2 versus 73 ± 1 mm for boys with normal genitals (P = 0.002). In these age-unmatched patient groups, there were also differences in age, height and weight (P = 0.0001, 0.0002 and 0.0004, respectively). After age matching (all <2 years of age), boys with hypospadias (n= 26) still featured a shorter AGD than boys with normal genitals (n= 26; 62 ± 2 versus 68 ± 2 mm respectively, P = 0.033) but the differences in age, height and weight were no longer significant.In humans, hypospadias may indeed be associated with reduced AGD. Additional studies are needed to corroborate these preliminary findings and to determine their etiology.

Men Who Seek Infertility Care May Not Represent the General US Population: Data From the National Survey of Family GrowthUROLOGYHotaling, J. M., Davenport, M. T., Eisenberg, M. L., Vandeneeden, S. K., Walsh, T. J.2012; 79 (1): 123-127

Abstract

To examine the National Survey of Family Growth to identify differences in the characteristics of men who did and did not seek infertility care to determine whether such men are representative of the U.S. population.We analyzed the data from the 2002 (cycle 6) National Survey of Family Growth. In-home interviews were conducted from March 2002 to February 2003. A total of 4928 men were surveyed, with underrepresented groups sampled at greater rates to provide an adequate sample size for meaningful statistical analyses. The use of infertility services was queried by a single question: "Have you been to a doctor to talk about ways to help have a baby together?" The demographic and socioeconomic variables, including age, marital status, number of children, race, religion, income, education, and insurance status were analyzed for the 2161 men surveyed who were aged 30-45 years. We performed bivariate and multivariate logistic regression analyses to determine the predictors of infertility service use.Marital status and education level were strongly associated with infertility care seeking. In the adjusted analysis, married men were 9 times (odds ratio 9.3, 95% confidence interval 4.1-20.9) more likely to seek care than unmarried men, and men with a college degree and those with an advanced degree were 3 times (odds ratio 2.7, 95% confidence interval 1.4-5.0) and 5 times (odds ratio 4.7, 95% confidence interval 2.1-10.5) more likely to seek care, respectively.Men seeking infertility care in the United States tend to be married, older, and more educated than those not seeking care. Given these findings, some results of male infertility studies from cohorts of men from infertility referral centers might not apply to the U.S. population.

Abstract

To determine whether Internet search volume for kidney stones has seasonal and geographic distributions similar to known kidney stone incidence.Google Insights for Search analyzes a portion of Google web searches from all Google domains to compute how many searches are performed for a given term relative to the total number of searches done over a specific time interval and geographic region. Selected terms related to kidney stones were examined to determine which most closely tracked kidney stone incidence. Google Insights for Search data were correlated with hospital admissions for the emergent treatment of nephrolithiasis found through the Nationwide Inpatient Sample. Ambient temperature in Seattle and New York were compared with search volume for these regions to display qualitative relationships.The term "kidney stones" had the highest seasonal correlation of terms examined (r = .81, P = .0014). Google Insights for Search output and national Inpatient Sample admissions also correlated when regions were compared (r = .90, P = .005). Qualitative relationships between ambient temperatures and kidney stone search volume do exist.Internet search volume activity for kidney stones correlates with temporal and regional kidney stone insurance claims data. In the future, with improved modeling of search detection algorithms and increased Internet usage, search volume has the potential to serve as a surrogate for kidney stone incidence.

Abstract

To determine the effect of income, education, and race on the use and outcomes of infertility care.Prospective cohort.Eight community and academic infertility practices.Three hundred ninety-one women presenting for an infertility evaluation.Face-to-face and telephone interviews and questionnaires.Use of infertility services and odds of pregnancy. Linear and logistic regression used to assess relationship between racial and socioeconomic characteristics, use of infertility services, and infertility outcomes.After adjustment for age and demographic and fertility characteristics, college-educated couples (? = $5,786) and households earning $100,000-$150,000 (? = $6,465) and ?$150,000 (? = $8,602) spent significantly more on infertility care than their non-college-educated, lower-income counterparts. Higher income and college-educated couples were much more likely to use more cycles of higher-intensity fertility treatment. The increased cost of infertility care was primarily explained by these differences in number and type of infertility treatment. Even after adjustment for these factors and total amount spent on fertility care, having a college degree was associated with persistently higher odds of achieving a pregnancy (OR = 1.9).Education and household income were independently associated with the amount of money spent on fertility care. This relationship was primarily explained by types and intensity of infertility treatments used. Having at least a college degree was independently associated with improved odds of pregnancy.

Abstract

Previous studies indicate that the sexual beliefs and mores of students in medical professions may influence their capacity to care for patients' sexuality and contraception issues. Students also represent a large sample of reproductive-age individuals. In this study, we examined contraceptive usage patterns in North American medical students.Students using online medical student social and information networks enrolled in allopathic and osteopathic medical schools in North America between February and July of 2008 were invited to participate via email and published announcements in an Internet-based survey consisting of a questionnaire that assessed ethnodemographic factors, year in school and sexual history. We also collected information about current use of contraceptive and barrier methods. Descriptive statistics and logistic regression were utilized to analyze responses.Among our 2269 complete responses, at least one form of contraception was being utilized by 71% of men and 76% of women. Condoms were the most popular form of contraceptive, utilized by 1011 respondents (50% of men and 40% of women). Oral contraceptive pills were the contraceptive of choice for 34% of men and 41% of women. Decreased rates of contraception use were associated with being black or Asian, not being in a relationship and having more sexual dysfunction in female respondents. Students who reported comfort discussing sexual issues with patients were more likely to use effective contraceptive methods themselves. Ten percent of this of sexually active medical students was not currently using contraception.There are significant differences in contraceptive use based on demographics, even at the highest education levels. The personal contraception choices of medical students may influence their ability to accurately convey information about contraception to their patients. In addition, medical students may personally benefit from improved knowledge of effective contraceptive practices.

Abstract

HIV/AIDS is a worldwide epidemic. Limited evidence suggests that men infected with HIV/AIDS are at increased risk for lower urinary tract symptoms. We determined whether HIV/AIDS status is an independent risk factor for self-reported bothersome lower urinary tract symptoms in a large contemporary cohort.We performed a cross-sectional, Internet based survey of urinary quality of life outcomes in adult HIV infected and HIV uninfected men who have sex with men. The main outcome measure was International Prostate Symptom Score.Of respondents with complete data 1,507 were HIV uninfected (median age 42 years, mean 43) and 323 HIV infected (median age 45 years, mean 45.1). Of the HIV infected respondents 148 were nonAIDS defining HIV infected and 175 were AIDS defining HIV infected. After adjusting for age and other comorbid conditions, nonAIDS defining HIV infected and AIDS defining HIV infected status increased the odds of severe lower urinary tract symptoms by 2.07 (95% CI 1.04-3.79) and 2.49 (95% CI 1.43-4.33), respectively. HIV infected men had a worse total International Prostate Symptom Score for all domains including quality of life compared to HIV uninfected men. Within the population of men with HIV, those with AIDS had worse mean total International Prostate Symptom Score and all individual International Prostate Symptom Score components relative to nonAIDS defining HIV infected men.HIV status is an independent risk factor for bothersome lower urinary tract symptoms. The odds of severe lower urinary tract symptoms are greater in HIV infected men with a history of AIDS.

Re: Estimating the Number of Vasectomies Performed Annually in the United States: Data From the National Survey of Family GrowthJOURNAL OF UROLOGYEisenberg, M. L., Lipshultz, L. I.2011; 185 (4): 1541-1542

Abstract

To examine resource use (costs) by women presenting for infertility evaluation and treatment over 18 months, regardless of treatment pursued.Prospective cohort study in which women were followed for 18 months.Eight infertility practices.Three hundred ninety-eight women recruited from infertility practices.Women completed interviews and questionnaires at baseline and after 4, 10, and 18 months of follow-up. Medical records were abstracted after 18 months to obtain details of services used.Per-person and per-successful-outcome costs.Treatment groups were defined as highest intensity treatment use. Twenty percent of women did not pursue cycle-based treatment; approximately half pursued IVF. Median per-person costs ranged from $1,182 for medications only to $24,373 and $38,015 for IVF and IVF-donor egg groups, respectively. Estimates of costs of successful outcomes (delivery or ongoing pregnancy by 18 months) were higher--$61,377 for IVF, for example--reflecting treatment success rates. Within the time frame of the study, costs were not significantly different for women whose outcomes were successful and women whose outcomes were not.Although individual patient costs vary, these cost estimates developed from actual patient treatment experiences may provide patients with realistic estimates to consider when initiating infertility treatment.

Abstract

This retrospective cohort study from a single clinical practice enrolled patients with evidence of calcified Peyronie's disease (PD) plaques detected on penile ultrasound at the time of initial presentation. The primary objective was to describe the effect of pentoxifylline (PTX) treatment on subtunical calcifications in men with PD. A PD-specific questionnaire was administered and sonographic evaluations were performed at baseline and follow-up visits. Descriptive statistics and ?(2) analysis were used to characterize the effect of PTX on calcified tunical plaques. In all, 71 men (mean age: 51.9 years) with PD and sonographic evidence of calcification were identified. Of them, 62 of these men were treated with PTX for a mean duration of 1 year, and nine with vitamin E or no treatment. Improvement or stabilization in calcium burden at follow-up was noted in 57 (91.9%) of men treated with PTX versus four (44.4%) of those not treated with PTX (P<0.001). PTX users were much less likely to have a subjective worsening of their clinical condition (25.0% versus 78.3%, P=0.002). Treatment with PTX appeared to stabilize or reduce calcium content in PD plaques. A randomized controlled trial is warranted to further explore this effect.

Abstract

An accurate assessment of the clinical stage of prostate cancer is important to determine the most appropriate treatments for patients. Most centers rely on digital rectal examination, given conflicting results in the literature regarding the role of transrectal ultrasonography (TRUS).Since ultrasound technologies as well as physician experience have improved, the contemporary impact of TRUS on the clinical staging of prostate cancer was assessed.In 2002, a standardized form to evaluate TRUS findings in order to rank the clinical suspicion of extracapsular extension (ECE) was used for all prostate cancer patients evaluated at UCSF. Preoperative clinical findings were compared with pathological staging as assessed by analysis of radical prostatectomy specimens from 2002 to 2007 (n = 620).Mean patient age was 58 ± 6.6 years with a mean PSA of 7.0 ± 4.5; 157/620 (25.3%) had pathologic ECE. Evidence of ECE by TRUS was associated with higher pathologic stage (P < 0.00001) and higher rates of biochemical failure after prostatectomy (P = 0.0006). Overall, TRUS had a 31% sensitivity, 92% specificity, 58% positive predictive value, and 80% negative predictive value with an area under the curve of 0.77 for the detection of ECE. TRUS alone was significantly more accurate in predicting ECE than commonly used nomograms or tables (P < 0.001) when examining patients with impalpable tumors.In the current era, TRUS provides an accurate method to assess a cancer stage.

Abstract

Depression and sexual dysfunction are often comorbid.We explored the relationship between sexuality, sexual dysfunction, and depressive symptoms in female medical students in North America.Female North American medical students were invited to participate in an internet survey. The CES-D was utilized to screen for depressive symptoms and an abbreviated Spielberger State-Trait Anxiety Index (STAI) was used to quantify anxiety symptoms.Subjects completed an ethnodemographic survey, a sexuality survey, and modified instruments for the quantification of sexual function (the Female Sexual Function Index [FSFI] and the Index of Sexual Life [ISL]). Multivariable logistic regression was used to explore the relationship between sexuality and depressive symptoms.There were 1,241 female subjects with complete data on CES-D and STAI. Mean age was 25.4 years. Depressive symptoms (CES-D>16) were present in 46% of respondents and were more common in subjects with anxiety symptoms. Subjects who were Caucasian, younger than 28, heterosexual, and in a relationship were least likely to report depressive symptoms. High risk of female sexual dysfunction (HRFSD) was significantly associated with greater likelihood of depressive symptoms (odds ratio [OR] 2.25, P<0.001). After adjusting for ethnodemographic and sexual history factors, HRFSD remained significantly positively associated with depressive symptoms (OR 1.85, P<0.001). Analysis of FSFI and ISL domains indicated that depressive symptoms were most directly associated with worse orgasmic function, interference in sex life from stress and lack of partner, and lower general life satisfaction (P<0.05). Interestingly, greater ISL-sexual satisfaction was associated with greater odds of depressive symptoms (OR 1.40, P=0.01).Depressive symptoms are common in female medical students. HRFSD is associated with depressive symptoms, although the relationship is complex when psychosocial factors are included in the multivariate model. Attention to sexuality factors from student health providers may enhance quality-of-life, academic achievement, and patient care.

Abstract

Ossified Peyronie's plaques may require surgical excision because of the palpable problems and penile curvature that result. As tunical excision can result in impotence and decrease penile sensation, we describe a novel method of tunical preserving excision of such lesions.We evaluated 12 men with dorsal penile curvature between 10° and 90°. Penile plaque size ranged from 1 to 5 cm. 80% had painful erections. An artificial erection was induced with intracavernous injection of papaverine to assess penile deformity. Via a circumcising or ventral incision, plication sutures were placed to correct penile curvature. A lateral longitudinal corporotomy was made and the calcified/ossified portion was dissected free from the tunica albuginea/plaque of the corpora cavernosa. Watertight tunical closure was then performed.Postoperatively, 80% of men reported erections always adequate for intercourse and normal sensation with a mean follow-up of 7 months (range 2.1-14.5 months). All patients required simultaneous penile plication to ensure a straight phallus. Pathologic evaluation of plaque specimens all showed bone fragments.Tunica-sparing excision of the ossified/calcified portion of Peyronie's plaques shows a durable benefit for large, ossified lesions and maintains potency and penile sensation.

Abstract

Prostate cancer treatment has the potential to lead to posterior urethral stricture. These strictures are sometimes recalcitrant to dilation and urethrotomy alone. We present our experience with the Urolume® stent for prostate cancer treatment related stricture.A total of 38 men with posterior urethral stricture secondary to prostate cancer treatment were treated with Urolume stenting. Stents were placed in all men after aggressive urethrotomy over the entire stricture. A successfully managed stricture was defined as open and stable for greater than 6 months after any necessary secondary procedures.The initial success rate was 47%. After a total of 31 secondary procedures in 19 men, including additional stent placement in 8 (18%), the final success rate was 89% at a mean ± SD followup of 2.3 ± 2.5 years. Four cases (11%) in which treatment failed ultimately requiring urinary diversion (3) or salvage prostatectomy (1). Incontinence was noted in 30 men (82%), of whom 19 (63%) received an artificial urinary sphincter a mean of 7.2 ± 2.4 months after the stent. Subanalysis revealed that irradiated men had longer strictures (3.6 vs 2.0 cm, p = 0.003) and a higher post-stent incontinence rate (96% vs 50%, p < 0.001) than men who underwent prostatectomy alone but the initial failure rate was similar (54% vs 50%, p = 0.4).Urolume stenting is a reasonable option for severe post-prostate cancer treatment stricture when patients are unwilling or unable to undergo open reconstructive surgery. Incontinence should be expected. The need for additional procedures is common and in some men may be required periodically for the lifetime of the stent.

Abstract

The association between varicoceles and male infertility has been known since the 1950s; however, the pathophysiology of the process remains uncertain. The primary proposed hypotheses involve hyperthermia, venous pressure, testicular blood flow, hormonal imbalance, toxic substances, and reactive oxygen species. It is difficult to identify a single or dominant factor, and it is likely that many of these factors contribute to the infertile phenotype seen in clinical practice. Moreover, patient lifestyle and genetic factors likely affect patient susceptibilities to the varicocele insult. While the current studies have weaknesses, they provide building blocks for futures studies into the pathophysiology of the varicocele.

Abstract

To determine the relationship between number of fertility treatment cycles and pregnancy rates.Prospective cohort study.Eight community and academic infertility practices.Four hundred eight (408) couples presenting for an infertility evaluation.Face-to-face and telephone interviews and questionnaires.Incidence of pregnancy. Cox regression analysis compared the efficacy of cycle-based fertility treatments with no cycle-based fertility treatment after multivariable adjustment.Couples using one to two medications-only cycles had a significantly higher pregnancy rate (hazard ratio [HR] 4.7 [95% confidence interval 1.3-16.6]), a benefit that did not persist after three or more cycles (HR 0.6 [0.1-3.2]). Couples using IUI for one (HR 2.9 [1.4-5.8]), two (HR 2.0 [0.9-4.5]), and three cycles (HR 4.5 [1.8-10.9]) were more likely to achieve a pregnancy. No additional benefit was seen for couples using four or more IUI cycles (HR 1.0 [0.4-2.6]). In vitro fertilization was associated with significant benefit for couples using one (HR 2.8 [1.5-5.2]) and two cycles (HR 2.2 [1.2-4.1]). Couples using three or more IVF cycles had a non-statistically significant higher likelihood of pregnancy (HR 1.3 [0.7-2.4]).Cycle-based fertility treatments may offer a point of diminishing returns for infertile couples: two cycles of medications only, three cycles of IUI, and two cycles of IVF.

Abstract

The role of sexuality as an association of medical student well-being has not been extensively studied.We explored the relationship between depressive symptoms, sexuality, and sexual dysfunction in male North American medical students.North American medical students were invited to participate in an Internet-based survey. The Center for Epidemiological Studies Depression Scale (CES-D) was utilized to screen for depressive symptoms.Subjects completed an ethnodemographic survey, a sexuality survey, and instruments for the quantification of anxiety, sexuality, and psychosocial function. Descriptive statistics, odds ratios (ORs), and logistic regression were used to analyze our data.There were 844 male subjects with complete data on the CES-D and the Spielberger State-Trait Anxiety Index. Depressive symptoms (CES-D ? 16) were present in 37% of respondents and were more common in subjects with greater levels of anxiety. Subjects who were in sexual relationships and/or had frequent sexual activity were less likely to be depressed compared to other subjects. Erectile dysfunction (ED) was associated with significantly greater likelihood of depressive symptoms (OR 2.90 and 9.27 for depressive symptoms in men with mild or moderate/severe ED relative to men without ED, P < 0.01). After adjusting for ethnodemographic and sexual history factors, ED remained significantly positively associated with depressive symptoms (OR 2.87 and 6.59 for depressive symptoms in men with mild or moderate/severe ED relative to men without ED after adjustment, P ? 0.01). Inclusion of data related to psychosocial/relationship factors in the multivariate model eliminated the significant association between ED and depressive symptoms (OR 1.59 and 2.29 for depressive symptoms in men with mild or moderate/severe ED relative to men without ED after adjustment with the Self-Esteem and Relationship quality instrument, P > 0.05), suggesting that psychosocial factors were more strongly associated with depressive symptoms than erectile function.Healthy sexuality and relationships may be protective against depressive symptoms in medical students. Attention to these factors may enhance medical student well-being.

Abstract

We studied a prospective cohort of 434 couples in Northern California and found that 13% did not pursue any form of infertility treatment after their initial consultation. Although age, education, and financial concerns remain important for patients in choosing whether to pursue infertility treatment, depressive symptoms may also be a barrier to achieving reproductive goals.

The impact of infertility on family size in the USA: data from the National Survey of Family GrowthHUMAN REPRODUCTIONBreyer, B. N., Smith, J. F., Shindel, A. W., Sharlip, I. D., Eisenberg, M. L.2010; 25 (9): 2360-2365

Abstract

Investigators have postulated that family size may be influenced by biologic fertility potential in addition to sociodemographic factors. The aim of the current study is to determine if a diagnosis of infertility is associated with family size in the USA.We analyzed data from the male and female samples of the 2002 National Survey of Family Growth using multivariable logistic regression models to determine the relationship between infertility and family size while adjusting for sociodemographic and reproductive characteristics.In the survey, 4409 women and 1739 men met the inclusion criteria, of whom 10.2% and 9.7%, respectively, were classified as infertile, on the basis of having sought reproductive assistance. Infertile females had a 34% reduced odds of having an additional child compared with women who did not seek reproductive assistance. For each additional 6 months it took a woman to conceive her first child, the odds of having a larger family fell by 9% and the odds of having a second child were reduced by 11%. A diagnosis of male infertility reduced the odds of having a larger family more than a diagnosis of female infertility.A diagnosis of infertility, especially male factor, is associated with reduced odds of having a larger family, implicating a biologic role in the determination of family size in the USA.

Abstract

To determine the views toward donor sperm and eggs of both men and women. The use of donor sperm or ova becomes an option for some infertile couples.Prospective cohort of infertile couples.Eight California reproductive endocrinology practices.Infertile couples (n=377) were recruited after an initial infertility clinic visit.From questionnaires administered at recruitment, ratings concerning the impact of the use of donor gametes were assessed. Differences between men and women in attitudes toward donor gametes were compared with analysis of variance (ANOVA). Linear regression was used to identify independent predictors of attitudes toward gametes.Women's attitudes toward donor sperm were significantly more negative than their attitudes toward donor eggs (5.1+/-1.4 vs. 4.7+/-1.6). Similarly, male donor gamete attitude scores were higher for donor sperm compared with donor eggs (4.9+/-1.6 vs. 4.1+/-1.6). Both men and women agreed that the use of donor sperm was more likely to have negative effects on their relationship and negative societal ramifications. Female donor gamete attitude scores were predicted by marital status, race, and education, whereas men's scores were independent of all measured factors.Both men and women view the use of donor sperm with more skepticism compared with the use of donor eggs, suggesting a unique underlying perception regarding the use of male donor gametes.

Abstract

There has been limited investigation of the sexuality and sexual dysfunction in non-heterosexual subjects by the sexual medicine community. Additional research in these populations is needed.To investigate and compare sexuality and sexual function in students of varying sexual orientations.An internet-based survey on sexuality was administered to medical students in North American between the months of February and July of 2008.All subjects provided information on their ethnodemographic characteristics, sexual orientation, and sexual history. Subjects also completed a series of widely-utilized instruments for the assessment of human sexuality (International Index of Erectile Function [IIEF], Female Sexual Function Index [FSFI], Premature Ejaculation Diagnostic Tool [PEDT], Index of Sex Life [ISL]).There were 2,276 completed responses to the question on sexual orientation. 13.2% of male respondents and 4.7% of female respondents reported a homosexual orientation; 2.5% of male and 5.7% of female respondents reported a bisexual orientation. Many heterosexual males and females reported same-sex sexual experiences (4% and 10%, respectively). Opposite-sex experiences were very common in the male and female homosexual population (37% and 44%, respectively). The prevalence of premature ejaculation (PEDT > 8) was similar among heterosexual and homosexual men (16% and 17%, P = 0.7, respectively). Erectile dysfunction (IIEF-EF < 26) was more common in homosexual men relative to heterosexual men (24% vs. 12%, P = 0.02). High risk for female sexual dysfunction (FSFI < 26.55) was more common in heterosexual and bisexual women compared with lesbians (51%, 45%, and 29%, respectively, P = 0.005).In this survey of highly educated young professionals, numerous similarities and some important differences in sexuality and sexual function were noted based on sexual orientation. It is unclear whether the dissimilarities represent differing relative prevalence of sexual problems or discrepancies in patterns of sex behavior and interpretation of the survey questions.

Abstract

To examine the relationship between body mass index and 24-hour urine constituents in a population of stone-forming patients.A total of 880 patients who presented to a metabolic stone clinic for initial evaluation were analyzed. Patients were stratified by gender and divided into quartiles of body mass index. Associations between body mass index (BMI) and urine parameters were explored using bivariate and multivariate linear regression.On bivariate analysis, increasing body mass index was associated with a significant increase in sodium, calcium, citrate, uric acid, magnesium, calcium oxalate, uric acid, and a decrease in pH in men. In women, it was associated with a significant increase in sodium, uric acid, oxalate, uric acid, and decreasing pH. On multivariate analysis, BMI was associated only with increases in sodium and calcium oxalate and decrease in pH in men. In women, multivariate analysis demonstrated positive association between BMI and urine sodium, creatinine, and phosphate and a negative relationship with urine citrate and sulfate.Increasing body mass index was related to several risk factors for urinary stone disease in this study, including increasing urine sodium and decreasing pH in men and increasing urine uric acid, sodium, and decreasing urine citrate in women. Just as general recommendations for patients with nephrolithiasis include high voided volumes, low dietary sodium, and low animal protein intake, perhaps weight reduction should be included as part of the counseling of stone-formers to optimize 24-hour urine parameters.

Abstract

To report two cases of secondary pulmonary hypertension resulting from microsphere extravasation following selective arterial embolization of renal angiomyolipoma, its diagnosis, and management.We reviewed the cases of two patients at the University of California, San Francisco, treated with selective arterial embolization for management of their angiomyolipoma (AML) using Tris-Acryl Gelatin Microspheres.Both patients were women, ages 51 and 77. Indications for treatment were the following: Patient 1 was treated for a large asymptomatic AML. Patient 2 was treated for a symptomatic, bleeding AML. Both patients developed progressive hypoxia following selective arterial embolization using Tris-Acryl Gelatin Microspheres. Each patient underwent a subsequent work up including a CT chest, echocardiogram, and chest x-ray. Both demonstrated significant pulmonary hypertension following their procedure and were discharged with supplemental oxygen.Selective arterial embolization of AML with microsphere extravasation into the pulmonary vasculature can lead to pulmonary hypertension and hypoxemia.

Abstract

To determine the prevalence of complementary and alternative medicine (CAM) use among couples seeking fertility care and to identify the predictors of CAM use in this population.Prospective cohort study.Eight community and academic infertility practices.A total of 428 couples presenting for an infertility evaluation.Interviews and questionnaires.Prevalence of complementary and alternative medicine therapy.After 18 months of observation, 29% of the couples had utilized a CAM modality for treatment of infertility; 22% had tried acupuncture, 17% herbal therapy, 5% a form of body work, and 1% meditation. An annual household income of > or = $200,000 (odds ratio 2.8, relative to couples earning

Abstract

To determine if the adjunctive use of power Doppler imaging (PDI) could provide prognostic utility in the treatment of prostate cancer, as an accurate prediction of the clinical behaviour of prostate cancer is important to determine appropriate treatment.Most centres rely on a digital rectal examination or transrectal ultrasonography (TRUS) to assess the clinical stage of patients. In 2002, we began using a standardized form to evaluate TRUS findings and PDI findings. We compared preoperative clinical findings with those from pathological analysis of 620 radical prostatectomy specimens from 2002 to 2007.The mean (sd) patient age was 58 (6.6) years with a mean prostate-specific antigen (PSA) level of 7.0 (4.5) ng/mL. Of the 620 specimens 157 (25.3%) had evidence of extracapsular extension on pathological evaluation; 443 (71.5%) men had a hypervascular lesion seen on TRUS, while 177 (28.5%) patients had none. There was no difference in preoperative PSA level, grade or stage of tumour. Furthermore, rates of biochemical recurrence or secondary treatment did not differ based on PDI findings. As a tool to help locate prostate tumours, PDI improved the specificity of TRUS but did not improve the overall accuracy or sensitivity.PDI provides little prognostic utility to assess risk in prostate cancer. However, PDI might improve the specificity of TRUS in identifying prostate tumours and could have a role in image guidance for focal therapy of prostate cancer.

Abstract

Traditionally, diagnosis and treatment plans for Peyronie's disease have been based on history and physical examination. Penile ultrasound provides rapid, anatomical information to establish disease severity, and to monitor progression and response to medical therapy. We determined the relationship between ultrasound characteristics and progression to surgical intervention in men with Peyronie's disease.We conducted a retrospective cohort study of 518 patients with Peyronie's disease. Patients completed a Peyronie's disease specific questionnaire detailing medical history, health related behaviors and Peyronie's disease characteristics, and underwent sonographic evaluation of the penis. Measurements of subtunical calcifications, septal fibrosis, tunical thickening (tunica thickness greater than 2 mm) and intracavernous fibrosis were made. Progression to surgery was determined from the medical record.In this cohort (mean patient age 53.8 years, range 20 to 78) 31% of patients had calcifications, 50% had tunical thickening, 20% had septal fibrosis and 15% had intracavernous fibrosis. Overall 25% of the cohort progressed to surgical intervention after an average followup of 1.25 years (range 0 to 7.6). Patients who underwent surgery were more likely to have subtunical calcifications present at the first clinic visit (OR 1.75, 95% CI 1.16-2.62). No other sonographic characteristics were associated with progression to surgery. After adjustment for age, marital status, degree of curvature, additional penile deformity, difficulty with penetration, ability to have intercourse and prior treatment for Peyronie's disease, calcifications were strongly associated with progression to surgery (OR 2.75, 95% CI 1.25-3.45).In a large cohort of patients with Peyronie's disease the presence of sonographically detected sub-tunical calcifications during the initial office evaluation was independently associated with subsequent surgical intervention.

Abstract

The prognostic meaning of an undetectable ultrasensitive prostate-specific antigen (USPSA) level after prostatectomy remains unclear.To determine whether an undetectable USPSA level obtained after surgery is a predictor of biochemical recurrence (BCR)-free survival.From the Urologic Oncology Database at the University of California San Francisco, 525 men were identified who had a USPSA measurement 1-3 mo postoperatively with at least 2 yr of follow-up. All preoperative and pathologic criteria were recorded.Patients were stratified based on their initial USPSA level. We defined an undetectable USPSA level at ?0.05 ng/ml. Recurrence was defined as two consecutive prostate-specific antigen (PSA) levels ?0.2 ng/ml or secondary treatment.We found that 456 patients (87%) had undetectable USPSA and 69 patients (13%) had detectable USPSA immediately postprostatectomy. A 5-yr recurrence-free rate of 86% was found in the undetectable USPSA group compared with 67% in the detectable USPSA group (p<0.01). For patients with pT3 disease, men with an undetectable USPSA had a 5-yr BCR-free survival rate of 78% compared with 40% for men with a detectable USPSA (p<0.01). A multivariable analysis confirmed that patients with an undetectable USPSA were 67% less likely to recur (hazard ratio: 0.33; 95% confidence interval: 0.20-0.55). As the detection level of PSA is lowered, the false-positive rate of BCR necessarily increases. A limitation of the study is its retrospective nature.An undetectable USPSA after radical prostatectomy is a prognostic indicator of BCR-free survival at 5 yr and may aid in predicting outcome in higher risk patients.

Abstract

Individuals who engage in regular sexual intercourse are more likely to report good overall quality of life. Studies of sexuality in adolescents have focused on high-risk behaviors whereas similar studies in older adults have focused on sexual dysfunction. Given a paucity of data on the sexual behaviors of young adults and the possibility of important relationships between sexuality and overall health, we sought to determine factors that influence the frequency of intercourse in adult men and women in the United States.To identify factors related to coital frequency in young and middle-aged adults.We analyzed data from the male and female sample of the 2002 National Survey of Family Growth to examine frequency of sexual intercourse among Americans aged 25-45 years (men: N = 2,469; women: N = 5,120).Multivariable negative binomial regression modeling was used to test for independent associations between the frequency of sexual intercourse and demographic, socioeconomic, and anthropometric variables.In this study, men and women between the ages of 25 and 45 have sex a mean 5.7 and 6.4 times per month, respectively. Being married significantly increased coital frequency for women but has no effect on male coital frequency. Increased height, less than high school education, and younger age were predictive of increased sexual frequency in men. Pregnancy was associated with significantly lower coital frequency for both men and women. No association was shown between self-reported health status and coital frequency on multivariable analysis.Among young male adults, coital frequency is associated with specific socioeconomic, demographic, and anthropomorphic characteristics. Sexual frequency in women does not appear to be influenced by such factors. Self-reported health is not predictive of sexual activity in this age group.

Abstract

To explore whether health care, socioeconomic, or personal characteristics account for disparities observed in the utilization of vasectomy. More than 500,000 vasectomies are performed annually in the United States. The safety and efficacy of vasectomy make it a good family planning option, yet the factors related to use of male surgical sterilization are not well understood. In this analysis, we examined differences in vasectomy rates according to factors such as race and socioeconomic status.We analyzed data from the male sample of the 2002 National Survey of Family Growth to examine the use of vasectomy among the sample of men aged 30-45 (n = 2161). Demographic, socioeconomic, and reproductive characteristics were analyzed to assess associations with vasectomy.About 11.4% of men aged 30-45 years reported having a vasectomy, representing approximately 3.6 million American men. Although 14.1% of white men had a vasectomy, only 3.7% of black and 4.5% of Hispanic men reported undergoing vasectomy. On multivariate analysis, a significant difference in the odds of vasectomy by race/ethnicity remained, with black (odds ratio = 0.20, 0.09-0.45) and Hispanic men (odds ratio = 0.41, 0.18-0.95) having a significantly lower rate of vasectomy independent of demographic, partner, and socioeconomic factors. Having ever been married, fathering 2 or more children, older age, and higher income were the factors associated with vasectomy.After accounting for reproductive history, partner, and demographic characteristics, black and Hispanic men were less likely to rely on vasectomy for contraception. Further research is needed to identify the reasons for these race/ethnic differences and to identify factors that impede minority men's reliance on this means of fertility control.

Abstract

A high body mass index increases the risk of nephrolithiasis in adults. Despite the growing problem of pediatric obesity, little is known about the relationship between body mass index and risk of nephrolithiasis in children. We examined the association between body mass index and 24-hour urine chemistry studies in children with a history of nephrolithiasis.A total of 43 children were included in the study. We retrospectively reviewed a database of 24-hour urine chemistry studies. We calculated body mass index for each individual and cases were then stratified by percentile. The 24-hour urine chemistry studies were adjusted for daily creatinine excretion, urine volume was adjusted for age, and pH and urine supersaturations were unadjusted.Body mass index percentile was below the 25th percentile in 8 cases, 25th to 49th percentile in 7, 50th to 74th percentile in 5 and 75th percentile or above in 14. On multivariate analysis the only 24-hour urine parameters with a significant relationship to body mass index were urine oxalate (negative relationship) and supersaturation of calcium phosphate (positive). As body mass index increased, urine oxalate excretion decreased and supersaturation of calcium phosphate increased.A high body mass index is associated with decreased urine oxalate and increased supersaturation of calcium phosphate. Given the increasing prevalence of obesity in younger patients, our findings have important clinical implications. Pediatricians and pediatric subspecialists should be aware of these findings when evaluating children with nephrolithiasis.

Who is the 40-Year-Old Virgin and Where Did He/She Come From? Data from the National Survey of Family GrowthJOURNAL OF SEXUAL MEDICINEEisenberg, M. L., Shindel, A. W., Smith, J. F., Lue, T. F., Walsh, T. J.2009; 6 (8): 2154-2161

Abstract

Little is known about young and middle aged adults who have never engaged in sexual intercourse. Individuals who have not engaged in sexual activity may theoretically have diminished overall quality of life, as recent evidence suggests that sexual activity may be related to overall health status in adults.We sought to identify factors related to sexual abstinence in young and middle-aged adults.We analyzed data from the male and female sample of the 2002 National Survey of Family Growth to examine sexual abstinence among unmarried participants aged 25-45 (men: N = 2,469; women: N = 5,120). Main Outcome Measures. Multivariable logistic regression modeling was used to test for independent associations between demographic, medical, and anthropometric variables and abstinence while adjusting for confounding and mediating variables.A total of 122 (13.9%) men aged 25-45 reported never having had sex, representing approximately 1.1 million American men in this age cohort. Among female participants, a total of 104 (8.9%) women aged 25-45 reported never having sex, representing approximately 800,000 American women in this age cohort. Both men and women who reported that they attend religious services one or more times per week were more likely to be sexually abstinent, independent of their specific religious beliefs. Virgin status was also significantly associated with drinking alcohol within the past year. While a college degree in women predicted virginity, education was not associated with virginity in men. Men showed lower rates of sexual abstinence if they reported having spent time in prison or serving in the military.Amongst young adults, sexual abstinence does not appear to be mediated by health status, anthropometric measures, or age. Attending religious services and avoidance of alcohol consumption are associated with virginity in adults. Other factors associated with abstinence differ between genders and merit further study.

Abstract

To review our experience with endoscopic extraction of renal foreign bodies. We assessed the preoperative factors associated with renal failure, operative planning and technique, and postoperative outcomes. Retained foreign bodies in the kidney from previous endoscopic and/or percutaneous manipulation can be technically challenging.We retrospectively reviewed our database from November 1992 through April 2008 for patients who had undergone extraction of a renal foreign body.A total of 21 patients were identified who met the selection criteria (11 men and 10 women), with a mean age of 41 +/- 22 years. The renal foreign bodies included indwelling ureteral stents (n = 15), nephrostomy tubes (n = 3), the inner core of a guidewire (n = 1), a nephrostomy tube pull string (n = 1), and a laser fiber (n = 1). Of the 21 patients, 15 (71%) required antegrade instrumentation by way of a percutaneous tract to remove the foreign body. Extraction of the nephrostomy pull string, fragmented guidewire, and laser fiber remnant were approached percutaneously. In the case of a retained ureteral stent, all but 2 required a combined antegrade and retrograde approach for extraction. Patients presenting with renal insufficiency (n = 5), defined by a creatinine >1.5 mg/dL, had obstruction resulting from a forgotten ureteral stent that had been left in place for among the longest periods in our cohort (range 1.5-10 years). Two fifths of these patients had improvement in renal function after endoscopic extraction.Patients with retained renal foreign bodies benefit from extraction by way of retrograde and/or antegrade endoscopic techniques. In patients presenting with renal failure, improvement in renal function is often seen after extraction of a retained renal foreign body.

Abstract

To determine whether obesity increases the risk of urethroplasty failure.A total of 381 patients underwent urethroplasty and had complete body mass index (BMI) data. Stricture recurrence-free survival was defined as subjective and objective improvement in urinary flow, an absence of radiographic evidence of stricture, and no further need for urethral instrumentation. Cox proportional hazards regression analysis was used to identify both univariate and multivariate predictors of urethroplasty outcome.The median patient age was 40 years (range 18-90). The median follow-up was 5.9 years (range 1 month to 10 years). Of the 381 patients, 60 developed recurrent stricture (15.7%). Overweight (BMI 25-30 kg/m(2)) and obese (BMI 30-35 kg/m(2)) patients were more likely to have urethroplasty failure, reaching significance and near significance on univariate and multivariate analysis, respectively (P = .03 and P = .07, respectively). Patients who were severely (BMI 35-40 kg/m(2)) or morbidly obese (BMI >40 kg/m(2)) did not have an increased risk of urethroplasty failure.Although obesity's relationship with urethroplasty failure is not linear, it does appear to affect outcomes after urethroplasty.

Abstract

Viscoat is a nonpyrogenic, sterile, viscoelastic solution used to protect the endothelium and enhance visualization during cataract and corneal surgery. Commonly used in ophthalmic surgery, we evaluated whether it could improve the optics during urologic microsurgery without adversely affecting outcomes.We retrospectively compared consecutive vasovasostomies performed by a single surgeon with (n = 23) and without (n = 50) the bilateral use of Viscoat. The examined parameters included patient age, vasectomy duration, intraoperative sperm characteristics, patency (ejaculation of motile sperm), time to patency, and postoperative semen characteristics. The comparisons of the sample mean values and proportions were assessed with analysis of variance, Wilcoxon, and chi(2) tests.Subjectively, Viscoat improved visualization of the vasal lumen and suture placement and aided in resident and fellow instruction. The vasovasostomy cases performed with and without the use of Viscoat were similar with regard to the patient and intraoperative characteristics. The overall patency rates were similar between the two groups (91% vs 92%, P = .92) with a median follow-up of 7 months. In addition, the best total motile sperm count and the durability of the patency achieved were similar between the two groups.Viscoat is a dispersive agent that does not adversely affect surgical patency after vasovasostomy. Subjectively, it helped with visualizing the lumen of the vas deferens during urologic microsurgery.

Abstract

Many patients present with bilateral stones. There is a unique group of patients, however, that presents with stones exclusively on one side. We hypothesize that in such situations, 24-hour urine collections may not reveal specific defects on the affected stone-bearing kidney. We therefore evaluated selective 12-hour urine collections after percutaneous nephrolithotomy (PNL) to help determine if there is differential renal excretion.We collected urine specimens from patients with nephrolithiasis who underwent unilateral PNL. Urine samples were collected and analyzed from nephrostomy tubes, representing the affected kidneys, and from Foley bladder catheters, representing the contralateral mate kidney.Thirty-one patients were studied (14 with unilateral nephrolithiasis and 17 with bilateral). Treated kidneys from patients with unilateral nephrolithiasis displayed lowered urine excretion of uric acid, sodium, chloride, calcium, and total osmoles when compared to patients with bilateral nephrolithiasis. Stone size and length of procedure were not predictive of urine composition after PNL.Treated kidneys from patients with a history of unilateral stone disease revealed marked differences in urine excretion compared to those with bilateral nephrolithiasis after unilateral PNL. These findings could be secondary to the surgical insult, urinary stone disease, or could be a responsible factor for stone pathogenesis.

Abstract

To determine the efficacy of partial cryoablation of the prostate in the salvage setting.All patients who were treated between April 2004 and September 2007 for recurrent prostate adenocarcinoma after failure of primary radiotherapy by means of partial cryoablation were identified.Nineteen patients met inclusion criteria; 15 had >6 months' follow-up. Mean age was 71 years. Men received salvage therapy a mean of 6 years after primary radiotherapy. Median follow-up was 18 months (range, 6-33 months). The biochemical recurrence-free survival rate (according to the American Society for Therapeutic Radiology and Oncology definition) was 89%, 67%, and 50% at 1, 2, and 3 years, respectively. One of 10 patients harbored residual carcinoma on routine follow-up biopsy at 1 year, whereas 50% harbored residual benign prostate tissue. Complications included incontinence (1), urethral stricture (1), and urethral ulcer (1).In properly selected patients with a unilateral focus of disease recurrence after radiotherapy, acceptable oncologic results can be achieved with partial cryoablation of the prostate, with low morbidity.

Abstract

Ejaculatory duct obstruction is a treatable cause of male infertility but the diagnosis can be difficult to make. Transrectal ultrasound is valuable but not specific for ejaculatory duct obstruction. Adjunctive procedures, such as chromotubation and seminal vesicle aspiration, are more sensitive but not definitive, especially for partial obstruction. We describe what is to our knowledge a new hydraulic test and report its ability to identify physical and functional ejaculatory duct obstruction.Two groups of men were studied, including patients with infertility or ejaculatory pain in whom ejaculatory duct obstruction was suspected and fertile men undergoing vasectomy reversal (controls). In each cohort ejaculatory duct injection and manometry were performed. Patients with ejaculatory duct obstruction underwent transurethral ejaculatory duct resection based on routine criteria. Pressure was reassessed after resection. Manometry pressures were compared between controls and patients with ejaculatory duct obstruction, and correlated with the response to transurethral ejaculatory duct resection.In the 7 controls (14 sides) mean ejaculatory duct opening pressure was 33.2 cm H(2)O. In the 9 patients (17 sides) with suspected ejaculatory duct obstruction mean ejaculatory duct opening pressure before transurethral ejaculatory duct resection was 116 cm H(2)O. In the 6 patients who underwent resection, which was unilateral and bilateral in 3 each, mean ejaculatory duct opening pressure decreased from 118 to 53 cm H(2)O. Of the 5 patients who underwent semen analyses before and after resection 80% showed an increase in ejaculate volume and/or at least 100% improvement in TMC (volume x concentration x motile fraction).Ejaculatory duct manometry with baseline values defined in fertile men demonstrates that men with clinically suspected ejaculatory duct obstruction have higher ejaculatory duct opening pressure than fertile men and ejaculatory duct pressure decreases after transurethral ejaculatory duct resection.

Abstract

To describe the current role of first-stage urethroplasty and its success as a management option in patients with complex anterior urethral stricture disease.We reviewed our urethral stricture database to identify patients managed with a staged urethral reconstruction or permanent first-stage urethroplasty. We noted patient age, etiology of stricture disease, location and length of stricture, location of neomeatus, indication for a staged approach, follow-up, and failure rate.A total of 38 men with a median age of 53 years met the inclusion criteria. The etiology of stricture disease varied, most commonly prior hypospadias repair (n = 9 [24%]) and lichen sclerosis (n = 6 [16%]). Location of stricture disease varied throughout the anterior urethra. Median stricture length was 5 cm. First-stage urethroplasty was accomplished with a penile shaft neomeatus in 13 patients (34%) and a perineal neomeatus in 25 (66%). Median follow-up was 22 months. Postoperative urethral dilation was required in 7 patients (18%). No patient has required an indwelling urethral catheter, suprapubic cystostomy, or urinary diversion. Of 38 patients, 9 (24%) have undergone a second-stage urethroplasty.The first-stage urethroplasty produces unobstructed voiding with few complications in high-risk patients. Few patients elect to have a second-stage urethroplasty performed. This is an old but not obsolete concept. We have presented modifications in technique to optimize success.

Abstract

We describe our experience with the management of restricture after urethral stent placement, including endoscopic and open surgical treatment.We surveyed our prospectively collected database for patients with restenosis after urethral stent insertion. We reviewed patient age, comorbidities, indications for stent placement, restricture length, management of restricture, postoperative complications and the further restenosis rate.Overall we have treated 22 patients with failed urethral stents with a median followup of 30 months (range 1 to 96). All stents were initially placed for urethral stricture management. Stricture etiology included prostate cancer therapy in 9 cases, idiopathic causes in 6, urethral instrumentation in 2, trauma in 2, simple prostatectomy in 2 and gender reassignment/phalloplasty in 1. Ten patients had anterior urethral stricture, 11 had posterior stricture and 1 patient had each type. Of the 22 patients with stenosis after stent placement 13 underwent urethroplasty. Of the 18 patients with indwelling stents at treatment the stent was removed in 8 intraoperatively and in 10 the stent was left in situ. Ten of the 11 anterior strictures were treated with urethroplasty. Only 4 of the 12 posterior strictures were treated with urethroplasty, while 8 were managed endoscopically. Our overall success rate for treatment after stent failure was 67% (8 of 12 cases) for posterior urethral strictures and 82% (9 of 11) for anterior strictures.Urethral stent failure requires complex intervention. A failed posterior urethral stent can often be managed endoscopically. Conversely we have managed failed anterior urethral stents by urethroplasty.

Abstract

Endocrine disruptors, such as environmental compounds with endocrine-altering properties, may cause hypospadias and cryptorchidism in several species, including humans. Anogenital distance is sexually dimorphic in many mammals, with males having longer anogenital distance on average than females. Animal models of proposed endocrine disruptors have associated prenatal exposure with hypospadias, cryptorchidism, and reduced anogenital distance. Human studies have correlated shorter anogenital distance to in utero exposure to putative endocrine disruptors. We review preliminary data suggesting that anogenital distance is reduced in boys with hypospadia and cryptorchidism. Hence, human hypospadias and cryptorchidism may be associated with reduced anogenital distance as a result of endocrine disruption.

Abstract

We report long-term outcomes and late complications after laparoscopic nephrectomy with autotransplantation.We retrospectively reviewed clinical data on all patients who underwent laparoscopic nephrectomy with autotransplantation between July 2000 and March 2007. Late complications, ie greater than 6 months, that required surgical intervention were analyzed. Clinical outcomes in patients with primary ureteral stricture disease and oncological outcomes in patients with renal tumors were examined.Indications for autotransplantation included complex ureteral stricture disease in 15 patients and renal malignancy in 4. Median age at surgery was 48 years (range 25 to 68). Median followup was 29 months. Of the 17 patients with greater than 6 months of followup late complications requiring surgical intervention occurred in 4. Transplant nephrectomy was required in 2 patients in the stricture group. Indications for nephrectomy were nonfunction complicated by pseudoaneurysm in 1 case and chronic loin pain in 1. Another patient had recurrent nephrolithiasis requiring percutaneous nephrolithotomy and in 1 a pseudoaneurysm was managed successfully by endovascular techniques. Two patients in the tumor group had disease progression, which was managed medically.Given the complexity and severity of disease that necessitates renal autotransplantation, it is not surprising that additional treatments are required. Patients with primary stricture disease may be at increased risk for vascular aneurysm due to infection and/or inflammation. Tumor progression is possible after ex vivo tumor excision and autotransplantation, especially in patients requiring heroic measures to avoid or delay dialysis. Thus, careful patient selection and vigilant followup are mandatory.

Abstract

Although rarely used today for supravesical urinary diversion, ureterosigmoidostomy remains useful in patients with bladder exstrophy. However, management of ureteral stricture and ureteral urolithiasis is challenging because of the lack of anatomic landmarks.We reviewed our prospectively collected database from 1994 to 2006 for all patients requiring surgical treatment for obstructive complications associated with ureterosigmoidostomy.Our analysis revealed 3 patients (mean age 46 years; 2 men and 1 woman). All 3 patients had undergone ureterosigmoidostomy as a component of bladder exstrophy management. All patients presented with renal failure due to obstruction and required antegrade endoscopic management. Two patients had anastomotic strictures and one had obstructive urolithiasis. One patient in whom the stricture was judged to be chronic was treated with an endoureterotomy and Acucise balloon. The second patient, who had an acute obstruction after colonoscopic biopsy of his anastomosis, was treated with antegrade balloon dilation. Both patients had stents placed across the anastomosis for 6 weeks postoperatively. Despite reflux of stool into the collecting system, neither patient manifested with local or systemic signs of infection. The patient with urolithiasis required antegrade basket stone extraction.Obstructive complications after ureterosigmoidostomy should be managed using antegrade endoscopic techniques.

Abstract

Current recommendations regarding posthumous sperm retrieval (PSR) are based on a small number of cases. Our purpose was to determine the time interval from death to a successful procedure.Seventeen consecutive PSR procedures in 14 deceased and 3 neurologically brain-dead patients at two male infertility centres [Sheba Medical Center (SMC), Tel-Hashomer, Israel and University of California San Francisco (UCSF), San Francisco, CA, USA] were analysed. Main outcome measures were retrieval of vital sperm, pregnancies and births.PSR methods included resection of testis and epididymis (n = 8), en-block excision of testis, epididymis and proximal vas deferens with vasal irrigation (n = 6), electroejaculation (EEJ) (n = 2) and epididymectomy (n = 1). PSR was performed 7.5-36 h after death. Sperm was retrieved in all cases and was motile in 14 cases. In two cases, testicular and epididymal tissues were cryopreserved without sperm evaluation, and in one case, no motility was detected. IVF and ICSI were performed in two cases in which sperm had been retrieved 30 h after death, and both resulted in pregnancies and live births.Viable sperm is obtainable with PSR well after the currently recommended 24-h time interval. PSR should be considered up to 36 h after death, following appropriate evaluation. No correlation was found between cause of death and chance for successful sperm retrieval.

Abstract

The hepatic glucose transporter, GLUT2, facilitates bidirectional glucose transport across the hepatocyte plasma membrane under insulin regulation. We studied the interactions of IR and GLUT2 proteins to determine whether they are physically coupled in a receptor-transporter complex. By comparing endosome and plasma membrane IR and GLUT2 ratios before and after feeding, it was determined that IR and GLUT2 are internalized in a fixed ratio. When solubilized hepatocytes were immunoprecipitated with antibodies against either IR or GLUT2, both proteins co-precipitated. The association of IR and GLUT2 was further assessed by confocal microscopy. Sections of fed liver were incubated with fluorescein-tagged anti-GLUT2 or Texas Red-tagged anti-IR. Colocalization was observed both at the plasma membrane and in the cytosol. Fluorescence-resonance energy transfer studies further confirmed this association. We conclude that IR and GLUT2 form a receptor-transporter complex in hepatocytes, which forms a mechanism of insulin-mediated hepatic glucose regulation.